Vanda's NEREUS cuts semaglutide vomiting in Phase 3 study

Vanda Pharmaceuticals said on Oct 27, 2026, that its drug NEREUS (tradipitant) reduced vomiting triggered by the GLP-1 drug semaglutide in a Phase 3 study, and that it intends to ask the FDA to add that use to the label. The company reported the topline numbers in a release issued at 6:50 a.m. ET. The full data set has not been published in a journal or presented at a meeting.

What the study tested

Study 3601, protocol number VP-VLY-686-3601, was a randomized, placebo-controlled trial. Participants took either tradipitant, an oral drug that blocks the neurokinin-1 (NK-1) receptor in the brain’s vomiting center, or a placebo. They then received one dose of semaglutide, the active ingredient in Wegovy, without titration, the gradual step-up in dose that doctors use when starting the drug.

Vanda says that choice was deliberate: an untitrated dose produces a high rate of vomiting, so it is a strict test of whether a preventive drug works. In its April announcement of the program, the company described the semaglutide dose used in its earlier Phase 2 study as one that normally takes 9 weeks of titration to reach.

The protocol number matches the ClinicalTrials.gov record for the Thetis study (NCT07446439), which Vanda announced in April. That record describes a double-blind Phase 3 trial in healthy volunteers with overweight or obesity, with an estimated enrollment of 280. The Oct 27 release does not use the Thetis name. In April, Vanda said it expected topline Thetis results by the fourth quarter of 2026.

What the results show

Vanda reported these rates for tradipitant versus placebo, with p-values adjusted for study site:

• Any vomiting (primary endpoint): 43.0% (61 of 142) versus 58.5% (96 of 164), p=0.006. Vanda calls this a 27% relative reduction.
• Vomiting plus severe nausea (key secondary endpoint): 33.1% (47 of 142) versus 50.6% (83 of 164), p=0.002, a 35% relative reduction. Severe nausea meant a worst nausea score of 3 or higher.

The company also reported two analyses that it labels exploratory and post hoc, meaning they were not the study’s planned endpoints:

• Frequent multi-day vomiting (more than 2 episodes on more than one day): 6.3% versus 15.9%, p=0.008.
• Extreme vomiting (more than 10 episodes in total): 2.8% versus 14.6%, p=0.0003.

Vanda said almost all vomiting in either group happened by Day 2. Rates peaked on Day 1, and the gap between the groups was widest on Days 1 and 2.

On safety, Vanda said only that tradipitant was “generally well tolerated” and that no new safety signals were seen. The release does not give adverse event rates.

“These results demonstrate that NEREUS can meaningfully reduce vomiting and frequent multi-day vomiting induced by GLP-1 therapy, which are key contributors to treatment discontinuation,” said Mihael H. Polymeropoulos, Vanda’s president, chief executive and board chairman.

A single dose, not everyday use

In clinical practice, semaglutide is started at a low dose and raised gradually. Study 3601 tested one untitrated dose. Vanda argues that a pooled exposure-response analysis of its Phase 2 and Phase 3 data found the drug’s effect held steady across the semaglutide levels observed, and that this supports applying the results to real-world use. The release does not include data from people on a standard, titrated course of treatment.

The earlier Phase 2 study used a similar design. In it, 29.3% of tradipitant participants (17 of 58) vomited, versus 58.6% on placebo (34 of 58), p=0.0016, according to Vanda’s April release.

The regulatory path

NEREUS is already on the market for a different use. Drugs@FDA lists its approval on Dec 30, 2025, and the FDA counted it among its novel drug approvals for 2025. It is approved to prevent vomiting induced by motion in adults. Vanda licensed tradipitant from Eli Lilly.

Vanda said it will discuss the results with the FDA and is planning a supplemental New Drug Application (sNDA) for preventing vomiting tied to GLP-1 receptor agonist therapy. The release’s risk language mentions the FDA’s willingness to meet with Vanda during 2027. In April, the company cautioned that more study data might be required before approval. Vanda is due to report third-quarter results on Oct 28.

What is not known

• The full results. Vanda has released topline figures only. Adverse event rates and a peer-reviewed report are not yet public.
• Everyday use. The study gave a single untitrated dose, and the trial registry describes healthy volunteers. Whether the effect is the same for patients on a usual titration schedule over months has not been reported.
• The FDA’s view. The agency has not said whether these data could support a new indication or whether it will ask for more studies. Vanda has not given a filing date.

NEREUS is not approved for nausea or vomiting caused by GLP-1 drugs. We will update this story if Vanda files its application or publishes the full data.